Richardson, R. A. K. | bioRxiv Science

bioRxiv2023

A Comprehensive Enumeration of the Human Proteostasis Network. 2. Components of the Autophagy-Lysosome Pathway

The condition of having a healthy, functional proteome is known as protein homeostasis, or proteostasis. Establishing and maintaining proteostasis is the province of the proteostasis network, approximately 2,700 components that regulate protein synthesis, folding, localization, and degradation. The proteostasis network is a fundamental entity in biology that is essential for cellular health and has direct relevance to many diseases of protein conformation. However, it is not well defined or annotated, which hinders its functional characterization in health and disease. In this series of manuscripts, we aim to operationally define the human proteostasis network by providing a comprehensive, annotated list of its components. We provided in a previous manuscript a list of chaperones and folding enzymes as well as the components that make up the machineries for protein synthesis, protein trafficking into and out of organelles, and organelle-specific degradation pathways. Here, we provide a curated list of 838 unique high-confidence components of the autophagy-lysosome pathway, one of the two major protein degradation systems in human cells.

bioinformatics↗

bioRxiv2023

Data-driven design of a tool to promote the investigation of understudied genes

Present-day publications on human genes primarily feature genes that already appeared in many publications prior to completion of the Human Genome Project in 2003. These patterns persist despite the subsequent adoption of high-throughput technologies, which routinely identify novel genes associated with biological processes and disease. Although several hypotheses for bias in the selection of genes as research targets have been proposed, their explanatory powers have not yet been compared. Our analysis suggests that understudied genes are systematically abandoned in favor of better-studied genes between the completion of -omics experiments and the reporting of results. Understudied genes remain abandoned by studies that cite these -omics experiments. Conversely, we find that publications on understudied genes may even accrue a greater number of citations. Among 45 biological and experimental factors previously proposed to affect which genes are being studied, we find that 33 are significantly associated with the choice of hit genes presented in titles and abstracts of - omics studies. To promote the investigation of understudied genes we condense our insights into a tool, find my understudied genes (FMUG), that allows scientists to engage with potential bias during the selection of hits. We demonstrate the utility of FMUG through the identification of genes that remain understudied in vertebrate aging. FMUG is developed in Flutter and is available for download at fmug.amaral.northwestern.edu as a MacOS/Windows app.

genomics↗